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The accuracy of computed tomography angiography (CTA) image interpretation depends on the radiologist. This study aims to develop a new method for automatically detecting intracranial aneurysms from CTA images using deep learning, based on a convolutional neural network (CNN) implemented on the DeepMedic platform. Ninety CTA scans of patients with intracranial aneurysms are collected and divided into two datasets: training (80 subjects) and test (10 subjects) datasets. Subsequently, a deep learning architecture with a three-dimensional (3D) CNN model is implemented on the DeepMedic platform for the automatic segmentation and detection of intracranial aneurysms from the CTA images. The samples in the training dataset are used to train the CNN model, and those in the test dataset are used to assess the performance of the established system. Sensitivity, positive predictive value (PPV), and false positives are evaluated. The overall sensitivity and PPV of this system for detecting intracranial aneurysms from CTA images are 92.3% and 100%, respectively, and the segmentation sensitivity is 92.3%. The performance of the system in the detection of intracranial aneurysms is closely related to their size. The detection sensitivity for small intracranial aneurysms (≤ 3 mm) is 66.7%, whereas the sensitivity of detection for large (> 10 mm) and medium-sized (3-10 mm) intracranial aneurysms is 100%. The deep learning architecture with a 3D CNN model on the DeepMedic platform can reliably segment and detect intracranial aneurysms from CTA images with high sensitivity.
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Aprendizado Profundo , Aneurisma Intracraniano , Humanos , Angiografia por Tomografia Computadorizada , Tomografia Computadorizada por Raios X/métodos , Angiografia Digital/métodos , Angiografia Cerebral/métodos , Sensibilidade e EspecificidadeRESUMO
As it is high in value, extra virgin olive oil (EVOO) is frequently blended with inferior vegetable oils. This study presents an optical method for determining the adulteration level of EVOO with soybean oil as well as peanut oil using LED-induced fluorescence spectroscopy. Eight LEDs with central wavelengths from ultra-violet (UV) to blue are tested to induce the fluorescence spectra of EVOO, peanut oil, and soybean oil, and the UV LED of 372 nm is selected for further detection. Samples are prepared by mixing olive oil with different volume fractions of peanut or soybean oil, and their fluorescence spectra are collected. Different pre-processing and regression methods are utilized to build the prediction model, and good linearity is obtained between the predicted and actual adulteration concentration. This result, accompanied by the non-destruction and no pre-treatment characteristics, proves that it is feasible to use LED-induced fluorescence spectroscopy as a way to investigate the EVOO adulteration level, and paves the way for building a hand-hold device that can be applied to real market conditions in the future.
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Arachis , Óleo de Soja , Contaminação de Alimentos/análise , Azeite de Oliva/análise , Óleos de Plantas/análise , Espectrometria de FluorescênciaRESUMO
The PROSPECT leaf optical radiative transfer models, including PROSPECT-MP, have addressed the contributions of multiple photosynthetic pigments (chlorophyll a and b, and carotenoids) to leaf optical properties, but photo-protective pigment (anthocyanins), another important indicator of vegetation physiological and ecological functions, has not been simultaneously combined within a leaf optical model. Here, we present a new calibration and validation of PROSPECT-MP+ that separates the contributions of multiple photosynthetic and photo-protective pigments to leaf spectrum in the 400-800 nm range using a new empirical dataset that contains multiple photosynthetic and photo-protective pigments (LOPEX_ZJU dataset). We first provide multiple distinct in vivo individual photosynthetic and photo-protective pigment absorption coefficients and leaf average refractive index of the leaf interior using the LOPEX_ZJU dataset. Then, we evaluate the capabilities of PROSPECT-MP+ for forward modelling of leaf directional hemispherical reflectance and transmittance spectra and for retrieval of pigment concentrations by model inversion. The main result of this study is that the absorption coefficients of chlorophyll a and b, carotenoids, and anthocyanins display the physical principles of absorption spectra. Moreover, the validation result of this study demonstrates the potential of PROSPECT-MP+ for improving capabilities in remote sensing of leaf photosynthetic pigments (chlorophyll a and b, and carotenoids) and photo-protective pigment (anthocyanins).
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Antocianinas , Carotenoides , Clorofila , Clorofila A , Folhas de Planta/fisiologiaRESUMO
In current off-axis system design process, optical path configuration (OPC) of the system often remains unchanged due to the explicit physical constraints added in the optimization process, and this prevents designers from obtaining potential better results with other OPCs. In this paper, we present a method to change the OPC automatically by ray-quadrangle-based optimization. In our method, a vector is utilized to represent the OPC and a penalty function based on the difference between the current vector and its target value is added into the optimization error function. During OPC variation, obscuration can be avoided without human interference. Examples are given as validation of the proposed method.
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X-ray luminescence tomography (XLT) is a promising imaging technology based on x-ray beams, with high-resolution capability. We developed a fan-beam XLT system, where the x-ray beam scans the object at predefined directions and positions. As the scanning at one position needs to cover the object, the data acquisition time is usually long. To improve spatial resolution, we propose a three-dimensional multiple-beam x-ray luminescence imaging method, in which the x rays are modulated by an x-ray fence-modulation component. The proposed method can produce multiple x-ray beams and ensure spatial resolution along the longitudinal direction as well as the transverse plane. The proposed methods of single-source experiments can achieve 0.62 mm in location error and 0.87 in the dice coefficient while 1.32 mm in location error and 0.63 in the dice coefficient in the double-source experiment. The simulation experiments show that our proposed method can achieve better results at different depths than the traditional scanning method. It is also demonstrated that the best simulation results can be achieved with the smallest x-ray width.
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Twenty four pyrazoline derivatives modified from Celecoxib were designed and synthesized as bi-inhibitor of COX-2 and B-Raf. They were evaluated for their COX-1/COX-2/B-Raf inhibitory and anti-proliferation activities. Compound A3 displayed the most potent activity against COX-2 and HeLa cell line (IC50=0.008 µM; GI50=19.86 µM) and showed superb COX-1/COX-2 selectivity (>500), being more potent and selective than positive control Celecoxib or 5-fluorouracil. Compounds A5 and B5 were introduced best B-Raf inhibitory activities (IC50=0.15 µM and 0.12 µM, respectively). Compound A4 retained superb bioactivity against COX-2 and HeLa cell line (IC50=0.015 µM; GI50=23.82 µM) and displayed moderate B-Raf inhibitory activity (IC50=3.84 µM). Docking simulation was conducted to give binding patterns. QSAR models were built using bioactivity data and optimized conformations to provide a future modification of COX-2/B-Raf inhibitors.
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Inibidores de Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Pirazóis/química , Sítios de Ligação , Celecoxib , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desenho de Fármacos , Feminino , Células HeLa , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas B-raf/metabolismo , Pirazóis/síntese química , Pirazóis/farmacologia , Relação Quantitativa Estrutura-Atividade , Sulfonamidas/química , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologiaRESUMO
Rapid detection of plant phenotypic traits is crucial for plant breeding and cultivation. Traditional measurement methods are carried out by rich-experienced agronomists, which are time-consuming and labor-intensive. However, with the increasing demand for rapid and high-throughput testing in tea plants traits, digital breeding and smart cultivation of tea plants rely heavily on precise plant phenotypic trait measurement techniques, among which hyperspectral imaging (HSI) technology stands out for its ability to provide real-time and rich-information. In this paper, we provide a comprehensive overview of the principles of hyperspectral imaging technology, the processing methods of cubic data, and relevant algorithms in tea plant phenomics, reviewing the progress of applying hyperspectral imaging technology to obtain information on tea plant phenotypes, growth conditions, and quality indicators under environmental stress. Lastly, we discuss the challenges faced by HSI technology in the detection of tea plant phenotypic traits from different perspectives, propose possible solutions, and envision the potential development prospects of HSI technology in the digital breeding and smart cultivation of tea plants. This review aims to provide theoretical and technical support for the application of HSI technology in detecting tea plant phenotypic information, further promoting the trend of developing high quality and high yield tea leaves.
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Salt stress is a well-known abiotic constraint that hampers crop productivity, affecting more than 424 million hectares of topsoil worldwide. Applying plant growth regulators externally has proven effective in enhancing crop resilience to salt stress. Previous metabolomics studies revealed an accumulation of Valine-Threonine-Isoleucine-Aspartic acid (VTID) in salt-stressed maize seedlings, suggesting its potential to assist maize adaptation to salt stress. To explore the effectiveness of VTID in enhancing salt tolerance in maize, 10 nM VTID was applied to salt-stressed maize seedlings. The results showed a remarkable 152.29% increase in plant height and a 122.40% increase in fresh weight compared to salt-stressed seedlings. Moreover, the addition of VTID enhanced the activity of antioxidant enzymes, specifically superoxide dismutase (SOD) and catalase (CAT), while reducing the level of malondialdehyde (MDA), a marker of oxidative stress. Additionally, VTID supplementation resulted in a significant increase in osmoregulatory substances such as proline. Metabolomic analysis revealed substantial changes in the metabolite profile of maize seedlings when treated with VTID during salt stress. Differential metabolites (DMs) analysis revealed that the identified DMs primarily belonged to lipids and lipid-like molecules. The receiver operating characteristic curve and linear regression analysis determined a correlation between isodolichantoside and the height of maize seedlings under salt-stress conditions. In conclusion, these findings validate that VTID effectively regulates tolerance in maize seedlings and offers valuable insights into the potential of short peptides for mitigating salt stress.
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OBJECTIVE: To explore the application value of preoperative multimodal image fusion technique in microvascular decompression (MVD) surgery via the suboccipital retrosigmoid approach. METHODS: Comprehensive data of 13 patients with primary trigeminal neuralgia (TN) and 13 patients with hemifacial spasm (HFS) treated by MVD surgery via the suboccipital retrosigmoid approach at the Department of Neurosurgery in Zhuhai People's Hospital from January 2021 to December 2021 were retrospectively analyzed. Preoperatively, all patients underwent cranial thin-section computed tomography and magnetic resonance examinations. Three-dimensional (3D) digital images of the skull, brainstem, nerves, and blood vessels were constructed by the 3D-slicer software or RadiAnt DICOM Viewer, which were then applied to design the surgical approach and surgical plan. The multimodal image fusion results, clinical characteristics, intraoperative data, surgical outcomes, and complications of all patients were summarized. RESULTS: The 3D digital images after fusion reconstruction can vividly show the anatomical relationship between the skull, brainstem, nerves, and blood vessels and was helpful to tailor the surgical strategy. All 26 patients underwent a smooth surgery. During the surgery, the key points were accurately located, the corners of the transverse sinus and sigmoid sinus were completely exposed, and no venous sinus injury occurred in all 26 patients. The key point was approximately located at the top point of the digastric groove, 12.3 ± 0.46 mm vertically above and 6.3 ± 0.6 mm laterally to the Frankfurt horizontal plane. The average cranial opening time was 30.4 (±3.6) min, and the mean operating time was 104.7 (±12.1) min. The diameter of the bone window was about 2.0 cm-3.0 cm, and the bone flap was restored. Among the 13 patients with primary TN, 12 (92.3%) exhibited complete relief of pain and 1 had significant relief. Complications of surgery included facial sensory numbness in 1 case, vertigo in 2 cases, and herpes at the corners of the mouth in 1 case. Of the 13 patients with HFS, 12 (92.3%) had complete relief of facial twitching symptoms and 1 had significant relief, and the complications included mild facial palsy in 2 (15.4%) cases and facial sensory numbness in another 2 (15.4%) cases. The mean follow-up time after surgery ranged from 6-16 months, and 1 of 26 patients experienced recurrence of HFS during the follow-up period. CONCLUSIONS: Preoperative multimodal image fusion technology can provide adequate preoperative assessment for patients and assistance in designing surgical approaches, which is an important guideline for MVD surgery via the suboccipital retrosigmoid approach for primary TN and facial muscle spasm.
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Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo , Humanos , Cirurgia de Descompressão Microvascular/métodos , Estudos Retrospectivos , Hipestesia/cirurgia , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Espasmo Hemifacial/diagnóstico por imagem , Espasmo Hemifacial/cirurgia , Resultado do TratamentoRESUMO
With continuous mutations of SARS-CoV-2 virus, new highly contagious and fast-spreading variants have emerged, including Delta and Omicron. The popular label-free immunosensor based on surface plasmon resonance (SPR) technique can be used for real-time monitoring of the ligand-analyte or antibody-antigen interactions occurring on the sensor surface. In this work, an SPR-based biosensor combined with a nanodisk array was presented to enhance the sensitivity toward virus detection. The nanodisk arrays were employed to enhance the adsorption of molecules for better detection by increasing the SPR field. Four optimal sensing configurations of silver or gold nanodisks on gold thin films with different aspect ratios were achieved through systematic optimization of all parameters to yield the best sensor performance. The resonance angle can be modulated simply by the aspect ratio of nanodisk array. The sensitivity of the optimized sensors has been improved, and the detection limit is smaller than that of bare gold-based sensor. The multi-jump resonance angle curves at tiny refractive index can clearly distinguish the difference of trace concentrations, which is very important for the accurate detection of trace substances. Supplementary Information: The online version contains supplementary material available at 10.1007/s11468-023-01802-3.
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Cervical cancer is a common malignancy that affects women worldwide. The long non-coding RNA (lncRNA) urothelial cancer-associated 1a (UCA1a) is reported to be significantly upregulated in cervical cancer. However, the exact role of UCA1a in cervical cancer remains unknown. This study aimed to identify two core promoter regions in UCA1a, which are essential for CEBPA-dependent transcription and FOXL1-, FOXL4-, and FOXL6-dependent activation, respectively. RNA sequencing results showed that overexpression of UCA1a resulted in extensive changes in the gene expression profile of HeLa cells, especially in the signaling pathway that regulates tumorgenesis. Mass spectrometry assay was conducted to show that pyruvate kinase M2 (PKM2) was a UCA1a-interacting protein. The 400 ~ 800 nt long region of UCA1a at the 5' end and the A1B domain of PKM2 were critical for the UCA1a-PKM2 interaction. Functional assays were performed to show that PKM2 was sufficient and necessary for UCA1a-induced proliferation of HeLa cells, which was partly due to the regulating of nuclear translocation and stabilization of PKM2. These findings provide a novel mechanism for UCA1a to regulate Hela cells by ubiquitination degradation of PKM2 and suggest that UCA1a may play a key role in the progression of cervical cancer.
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RNA Longo não Codificante , Neoplasias do Colo do Útero , Humanos , Feminino , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/patologia , Células HeLa , Linhagem Celular Tumoral , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Tea is one of the most common beverages in the world. In order to reduce the cost of artificial tea picking and improve the competitiveness of tea production, this paper proposes a new model, termed the Mask R-CNN Positioning of Picking Point for Tea Shoots (MR3P-TS) model, for the identification of the contour of each tea shoot and the location of picking points. In this study, a dataset of tender tea shoot images taken in a real, complex scene was constructed. Subsequently, an improved Mask R-CNN model (the MR3P-TS model) was built that extended the mask branch in the network design. By calculating the area of multiple connected domains of the mask, the main part of the shoot was identified. Then, the minimum circumscribed rectangle of the main part is calculated to determine the tea shoot axis, and to finally obtain the position coordinates of the picking point. The MR3P-TS model proposed in this paper achieved an mAP of 0.449 and an F2 value of 0.313 in shoot identification, and achieved a precision of 0.949 and a recall of 0.910 in the localization of the picking points. Compared with the mainstream object detection algorithms YOLOv3 and Faster R-CNN, the MR3P-TS algorithm had a good recognition effect on the overlapping shoots in an unstructured environment, which was stronger in both versatility and robustness. The proposed method can accurately detect and segment tea bud regions in real complex scenes at the pixel level, and provide precise location coordinates of suggested picking points, which should support the further development of automated tea picking machines.
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Soil salinization is an important worldwide environmental problem and the main reason to reduce agricultural productivity. Recent findings suggested that histidine is a crucial residue that influences the ROS reduction and improves the plants' tolerance to salt stress. Herein, we conducted experiments to understand the underlying regulatory effects of histidine on maize root system under salt stress (100 mM NaCl solution system). Several antioxidant enzymes were determined. The related expressed genes (DEGs) with its pathways were observed by Transcriptome technologies. The results of the present study confirmed that histidine can ameliorate the adverse effects of salt stress on maize root growth. When the maize roots exposed to 100 mM NaCl were treated with histidine, the accumulation of superoxide anion radicals, hydrogen peroxide, and malondialdehyde, and the content of nitrate nitrogen and ammonium nitrogen were significantly reduced; while the activities of superoxide dismutase, peroxidase, catalase, nitrate reductase, glutamine synthetase, and glutamate synthase were significantly increased. Transcriptome analysis revealed that a total of 454 (65 up-regulated and 389 down-regulated) and 348 (293 up-regulated and 55 down-regulated) DEGs were observed when the roots under salt stress were treated with histidine for 12 h and 24 h, respectively. The pathways analysis of those DEGs showed that a small number of down-regulated genes were enriched in phytohormone signaling and phenylpropanoid biosynthesis at 12 h after histidine treatment, and the DEGs involved in the phytohormone signaling, glycolysis, and nitrogen metabolism were significantly enriched at 24 h after treatment. These results of gene expression and enzyme activities suggested that histidine can improve the salt tolerance of maize roots by enriching some DEGs involved in plant hormone signal transduction, glycolysis, and nitrogen metabolism pathways.
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Objective: We retrospectively assessed the surgical results of PBC with preoperative multimodal image fusion and intraoperative Dyna Computed Tomography (CT) in 24 patients with primary trigeminal neuralgia (PTN) to explore a valuable aid for Percutaneous balloon compression (PBC). Methods: We studied the data of 24 patients with PTN. All patients underwent PBC and were assessed with preoperative multimodal image fusion [computed tomography (CT) and magnetic resonance imaging (MRI)] and intraoperative Dyna CT in the Department of Neurosurgery of Zhuhai People's Hospital between October 2020 and September 2021. Multimodal image fusion-three-dimensional (3D) reconstruction of CT and MRI data-was performed using 3D-Slicer software, and preoperative evaluation was performed according to the results of image fusion. Dyna CT was used to dynamically observe the position and shape of the metallic hollow introducer and Fogarty catheter and balloon during the operation to guide the operation in real time. We performed follow-up assessments each month and summarized the clinical characteristics, surgical effects, and complications in all patients. Results: Surgery was successful for all patients; the patients reported immediate pain relief. Surgical complications included facial numbness in 24 patients (100%), mild masseter weakness in three (12.5%), herpes zoster in three (12.5%), and balloon rupture in one (4.2%). None of the patients had serious surgical complications. The mean follow-up time was 9.6 ± 2.7 months. During the follow-up period, 22 patients (91.7%) experienced no recurrence of pain, and two patients (8.3%) experienced recurrence of pain, of which one underwent secondary PBC surgery. Conclusions: Preoperative multimodal image reconstruction can help fully evaluate PBC surgery, clarify the etiology, and predict the volume of contrast medium required during the operation. It provided important assistance for PBC treatment of trigeminal neuralgia patients when preoperative multimodal image fusion is combined with intraoperative Dyna CT.
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Objectives: To analyze the surgical effects of resecting skull base tumors using multimodal three-dimensional (3D) image fusion technology in the neurosurgery department and present some typical cases. Methods: From October 2019 to October 2021, we included 47 consecutive patients with skull base tumors in the Neurosurgery Department at Zhuhai People's Hospital in this study. Pre-operative head computed tomography and magnetic resonance imaging data acquisition was performed using the GE AW workstation software for registration fusion, image fusion, and 3D reconstruction. The surgical approach and surgical plan were designed based on the multimodal 3D image, and the resection rate, complication rate, and operative time of the surgery using the multimodal image fusion technique were analyzed. Results: The reconstructed multimodal 3D images precisely demonstrated the size, location, and shape of the tumor along with the anatomical relationship between the tumor and surrounding structures, which is consistent with the intraoperative findings. Among 47 patients, 39 patients (78.7%) underwent total resection, 5 (14.9%) underwent subtotal resection, and 3 (6.4%) underwent partial resection. The mean operative time was 4.42 ± 1.32 h. No patient died during the inpatient period. Post-operative complications included 6 cases of cerebrospinal fluid leakage (14.9%), 3 cases of intracranial infection (6.4%), 6 cases of facial paralysis (12.8%), 2 cases of dysphagia (4.3%), and 1 case of diplopia (2.1%), all of which were improved after symptomatic treatment. The application value of pre-operative 3D image fusion technology was evaluated as outstanding in 40 cases (85.1%) and valuable in 7 cases (14.9%). Conclusions: Pre-operative multimodal image fusion technology can provide valuable visual information in skull base tumor surgery and help neurosurgeons design the surgical incision, choose a more rational surgical approach, and precisely resect the tumor. The multimodal image fusion technique should be strongly recommended for skull base tumor surgery.
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OBJECTIVE: In this study, we aimed to investigate the function of microRNA-373-3p (miR-373-3p) in the pathogenesis of cervical cancer. METHODS: Human and mouse cervical cancer cell lines were transfected with miR-373-3p mimic and inhibitor. Cell proliferation and viability were evaluated with Cell Counting Kit-8 (CCK-8) assay and Lactate Dehydrogenase (LDH) assay, respectively. The AKT1-targeting role of miR-373-3p was analyzed by qPCR and Western blot. Finally, a mouse xenograft cervical tumor model was adopted to study the in vivo effect of miR-373-3p on tumor growth and the expression of AKT1. RESULTS: Over-expression of miR-373-3p significantly reduced the proliferation of cervical carcinoma cell line in vitro. In addition, miR-373-3p overexpression also inhibited cervical cancer growth in tumor-bearing mice. Mechanistically, we found that AKT1 gene can be targeted by miR-373-3p. MiR-373-3p mimic decreased the mRNA and protein expression of AKT1, while the miR-373-3p inhibitor increased the level of AKT1 in cervical cancer cells. AKT1 overexpression rescued the proliferation of cervical cancer cells transfected with miR-373-3p. CONCLUSION: MiR-373-3p can serve as a novel anti-tumor microRNA in cervical cancer by targeting AKT1.
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Proliferação de Células/genética , MicroRNAs/fisiologia , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias do Colo do Útero/patologia , Animais , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias do Colo do Útero/enzimologiaRESUMO
Digital holography is a well-accepted method for phase imaging. However, the phase of the object is always embedded in aberrations. Here, we present a digital holographic phase imaging with the aberrations fully compensated, including the high order aberrations. Instead of using pre-defined aberration models or 2D fitting, we used the simpler and more flexible 1D fitting. Although it is 1D fitting, data across the whole plane could be used. Theoretically, all types of aberrations can be compensated with this method. Experimental results show that the aberrations have been fully compensated and the pure object phase can be obtained for further studies.
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Cervical cancer is one of the most lethal malignancies amongst women, partially because it is unresponsive to many chemotherapeutic drugs. The mechanism underlying cisplatin (DDP) resistance in cervical cancer remains largely elusive. In this study, by detecting the 12 most reported down-regulated miRNAs in chemotherapy-sensitive and -resistant cervical cancer cells, we found that miR-497 was significantly reduced in chemotherapy-resistant HeLa/DDP cells and contributed to DDP chemosensitivity. Transketolase (TKT), a thiamine-dependent enzyme that plays a role in the channeling of excess glucose phosphates to glycolysis in the pentose phosphate pathway, was identified as a direct target of miR-497. TKT expression in clinical specimens was characterized by immunohistochemistry and the result showed that TKT was highly expressed in 81.1% (60/74) of samples examined. Data from Oncomine databases revealed that TKT was significantly up-regulated in cervical cancer tissues compared to normal controls. Gain-of-function and loss-of-function studies showed that the miR-497/TKT axis was a critical modulator in DDP chemosensitivity as demonstrated by cell viability and apoptosis assays. Mechanistically, DDP chemosensitivity induced by the miR-497/TKT axis was associated with glutathione (GSH) depletion and reactive oxygen species (ROS) generation, and GSH treatment effectively abrogated miR-497/TKT-mediated chemosensitivity. In conclusion, these findings suggest that a deregulated miR-497/TKT axis has important implications in the cervical cancer cellular response to DDP, and thus targeting this axis may be a promising way to improve chemosensitivity in cervical cancer.
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MicroRNAs (miRNA) play crucial roles in regulating cell proliferation, differentiation and developmental timing. Aberrantly expressed miRNAs have recently emerged as key regulators of metabolism. However, little is known about its role in tumor metabolism of cervical cancer. In this study, we determined the oncogenic effects of miRNAs on Warburg effect, a metabolic phenotype that allows cancer cells to utilize glucose even under aerobic conditions. A gain-of-function study was performed in 12 down-regulated miRNAs that frequently reported in cervical cancer. We found that miR-34a plays a suppressive role in Warburg effect as evidenced by decreased lactate production and glucose consumption. Knockdown of oncoprotein E6 expression of human papillomavirus in SiHa and HeLa cells by siRNAs lead to an increased protein level of p53, decreased level of miR-34a, as well as reduced Warburg effect. Subsequently, lactate dehydrogenase A (LDHA), which catalyzes the last key step in glycolysis, was identified as a direct target of miR-34a. Silencing of LDHA or introduction of miR-34a significantly attenuated colony formation ability and invasive capacity of SiHa and HeLa cells, and these effects were fully compromised by reintroduction of LDHA. In conclusion, our findings demonstrated that deregulated miR-34a/LDHA axis induced by HPV E6/p53 signaling facilitates tumor growth and invasion through regulating Warburg effect in cervical cancer, and provided new insights into the mechanism by which miR-34a contributes to the development and progression of cervical cancer.
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BACKGROUND: Infection with hepatitis B virus (HBV) during pregnancy may lead to perinatal transmission. OBJECTIVES: To compare the efficacy and safety of telbivudine versus lamivudine in interrupting perinatal transmission of hepatitis B virus. STUDY DESIGN: All pregnant women enrolled in this study were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Test patients underwent antiviral therapy with telbivudine or lamivudine while control patients received hepatitis B immune globulin (HBIG) injection. RESULTS: Patients in the telbivudine group had significantly lower HBV DNA and HBeAg levels and higher HBV DNA negative conversion rates compared to those in the lamivudine group before delivery. HBV DNA negative conversion rates in patients with abnormal alanine aminotransferase (ALT) levels were significantly higher than those in patients with normal ALT levels in the telbivudine and lamivudine groups before delivery. The intrauterine HBV infection rate and the percentage of immunization failure were both 0% in the telbivudine and lamivudine groups (χ(2)=0, 0; P=1, 1 respectively), compared to both 5% in the HBIG group (χ(2)=11.83, 7.86; P=0.002, 0.009 respectively). The side effects of three groups in mother and child were all unobvious. CONCLUSIONS: Telbivudine and lamivudine can reduce HBV DNA levels in pregnant women, interrupt the vertical transmission of HBV and be used safely in mothers and children.